Annals of Surgical Oncology

, Volume 26, Issue 2, pp 329–335 | Cite as

Multifocal/Multicentric Ipsilateral Invasive Breast Carcinomas with Similar Histology: Is Multigene Testing of All Individual Foci Necessary?

  • Anne GrabenstetterEmail author
  • Edi Brogi
  • Joanne F. Chou
  • Monica Morrow
  • Maura Dickler
  • Larry Norton
  • Hannah Y. Wen
Breast Oncology



Multiple synchronous ipsilateral invasive breast carcinomas (BCs) with similar histology usually have concordant receptor status. It is unknown whether individual foci with similar histology also share molecular and biological similarities or are heterogenous. This study examined the concordance of the 21-gene recurrence score (RS) in multiple synchronous morphologically similar ipsilateral BCs.

Patients and Methods

We identified patients with multiple ipsilateral BCs and available RS treated at our institution from 1/2014 to 6/2018. BCs were divided into three groups based on RS: (1) RS in same risk category, (2) RS in different risk categories but within 2-unit difference (e.g., RS 17 and RS 19), and (3) RS in different risk categories and a change of > 2 units. BCs in groups 1 and 2 were considered as concordant (no significant clinical impact) and BCs in group 3 as discordant (variation affects management).


A total of 53 patients met the study criteria. RS was concordant in 46 (87%) cases. Seven (13%) cases were discordant (group 3). Of these, three (43%, 3/7) had biopsy cavity changes (BXC) adjacent to the BC with highest RS. In two cases the focus with higher RS had a lower percentage of progesterone receptor-positive tumor cells. In two cases, extensive ductal carcinoma in situ was associated with the BC focus with lower RS.


Morphologically similar multifocal ipsilateral BCs have concordant RS in 87% (46/53) of cases. Our results suggest that, in cases of morphologically similar multifocal BCs, testing of a single focus provides accurate prognostic and predictive information.



We thank Ms. Donna Thompson for her invaluable assistance with data collection.


MM and MD have consulted for Genomic Health.


  1. 1.
    Houssami N, Ciatto S, Macaskill P, et al. Accuracy and surgical impact of magnetic resonance imaging in breast cancer staging: systematic review and meta-analysis in detection of multifocal and multicentric cancer. J Clin Oncol. 2008;26(19):3248–58.CrossRefGoogle Scholar
  2. 2.
    Wilkinson LS, Given-Wilson R, Hall T, Potts H, Sharma AK, Smith E. Increasing the diagnosis of multifocal primary breast cancer by the use of bilateral whole-breast ultrasound. Clin Radiol. 2005;60(5):573–8.CrossRefGoogle Scholar
  3. 3.
    Salgado R, Aftimos P, Sotiriou C, Desmedt C. Evolving paradigms in multifocal breast cancer. Semin Cancer Biol. 2015;31:111–8.CrossRefGoogle Scholar
  4. 4.
    Andea AA, Wallis T, Newman LA, Bouwman D, Dey J, Visscher DW. Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma. Cancer. 2002;94(5):1383–90.CrossRefGoogle Scholar
  5. 5.
    Buggi F, Folli S, Curcio A, et al. Multicentric/multifocal breast cancer with a single histotype: is the biological characterization of all individual foci justified? Ann Oncol. 2012;23(8):2042–6.CrossRefGoogle Scholar
  6. 6.
    Choi Y, Kim EJ, Seol H, et al. The hormone receptor, human epidermal growth factor receptor 2, and molecular subtype status of individual tumor foci in multifocal/multicentric invasive ductal carcinoma of breast. Hum Pathol. 2012;43(1):48–55.CrossRefGoogle Scholar
  7. 7.
    Dawson PJ, Baekey PA, Clark RA. Mechanisms of multifocal breast cancer: an immunocytochemical study. Hum Pathol. 1995;26(9):965–9.CrossRefGoogle Scholar
  8. 8.
    Middleton LP, Vlastos G, Mirza NQ, Eva S, Sahin AA. Multicentric mammary carcinoma: evidence of monoclonal proliferation. Cancer. 2002;94(7):1910–16.CrossRefGoogle Scholar
  9. 9.
    Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.CrossRefGoogle Scholar
  10. 10.
    Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.CrossRefGoogle Scholar
  11. 11.
    Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.CrossRefGoogle Scholar
  12. 12.
    Sparano JA. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer. 2006;7(4):347–50.CrossRefGoogle Scholar
  13. 13.
    Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111–21.CrossRefGoogle Scholar
  14. 14.
    Gradishar WJ, Anderson BO, Balassanian R, et al. NCCN guidelines insights: breast cancer, version 1.2017. J Natl Compr Canc Netw. 2017;15(4):433–51.CrossRefGoogle Scholar
  15. 15.
    Harris LN, Ismaila N, McShane LM, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(10):1134–50.CrossRefGoogle Scholar
  16. 16.
    Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer–Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290–303.CrossRefGoogle Scholar
  17. 17.
    Amin M, Edge, S, Green, F, et al., editors. AJCC cancer staging manual. 8th ed. Chicago, IL:Springer; 2017.Google Scholar
  18. 18.
    Cronin M, Sangli C, Liu ML, et al. Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer. Clin Chem. 2007;53(6):1084–91.CrossRefGoogle Scholar
  19. 19.
    Oncotype IQ (2018) Oncotype DX breast recurrence score information for healthcare professionals. Accessed 31 Aug 2018.
  20. 20.
    Lester SC, Bose S, Chen YY, et al. Protocol for the examination of specimens from patients with invasive carcinoma of the breast. Arch Pathol Lab Med. 2009;133(10):1515–38.Google Scholar
  21. 21.
    Baehner F QC, Pomeroy C, Cherbavaz D, Shak S. Biopsy cavities in breast cancer specimens: impact on quantitative RT-PCR gene expression profiles and recurrence risk assessment (abstract). Mod Pathol. 2009;22:28A–9A.Google Scholar
  22. 22.
    Allison KH, Kandalaft PL, Sitlani CM, Dintzis SM, Gown AM. Routine pathologic parameters can predict Oncotype DX recurrence scores in subsets of ER positive patients: who does not always need testing? Breast Cancer Res Treat. 2012;131(2):413–24.CrossRefGoogle Scholar
  23. 23.
    Hanna MG, Bleiweiss IJ, Nayak A, Jaffer S. Correlation of Oncotype DX recurrence score with histomorphology and immunohistochemistry in over 500 patients. Int J Breast Cancer. 2017;2017:1257078.CrossRefGoogle Scholar
  24. 24.
    Hou Y, Zynger DL, Li X, Li Z. Comparison of Oncotype DX with modified Magee equation recurrence scores in low-grade invasive carcinoma of breast. Am J Clin Pathol. 2017;148(2):167–72.CrossRefGoogle Scholar
  25. 25.
    Acs G, Esposito NN, Kiluk J, Loftus L, Laronga C. A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high oncotype DX recurrence scores in low-grade invasive breast carcinomas. Mod Pathol. 2012;25(4):556–66.CrossRefGoogle Scholar
  26. 26.
    Sparano JA, Paik S. Development of the 21-gene assay and its application in clinical practice and clinical trials. J Clin Oncol. 2008;26(5):721–8.CrossRefGoogle Scholar
  27. 27.
    Ahmed SS, Thike AA, Zhang K, Lim JC, Tan PH. Clinicopathological characteristics of oestrogen receptor negative, progesterone receptor positive breast cancers: re-evaluating subsets within this group. J Clin Pathol. 2017;70(4):320–6.CrossRefGoogle Scholar
  28. 28.
    Chaudhary LN, Jawa Z, Szabo A, Visotcky A, Chitambar CR. Relevance of progesterone receptor immunohistochemical staining to Oncotype DX recurrence score. Hematol Oncol Stem Cell Ther. 2016;9(2):48–54.CrossRefGoogle Scholar
  29. 29.
    Rakha EA, El-Sayed ME, Green AR, et al. Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol. 2007;25(30):4772–8.CrossRefGoogle Scholar
  30. 30.
    Tang P, Wang J, Hicks DG, et al. A lower Allred score for progesterone receptor is strongly associated with a higher recurrence score of 21-gene assay in breast cancer. Cancer Invest. 2010;28(9):978–82.CrossRefGoogle Scholar
  31. 31.
    Clark BZ, Dabbs DJ, Cooper KL, Bhargava R. Impact of progesterone receptor semiquantitative immunohistochemical result on Oncotype DX recurrence score: a quality assurance study of 1074 cases. Appl Immunohistochem Mol Morphol. 2013;21(4):287–91.CrossRefGoogle Scholar
  32. 32.
    Karsten M, Stempel M, Radosa J, Patil S, King TA. Oncotype DX in bilateral synchronous primary invasive breast cancer. Ann Surg Oncol. 2016;23(2):471–6.CrossRefGoogle Scholar
  33. 33.
    Toole MJ, Kidwell KM, Van Poznak C. Oncotype DX results in multiple primary breast cancers. Breast Cancer (Auckl). 2014;8:1–6.Google Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Anne Grabenstetter
    • 1
    Email author
  • Edi Brogi
    • 1
  • Joanne F. Chou
    • 2
  • Monica Morrow
    • 3
  • Maura Dickler
    • 4
  • Larry Norton
    • 5
  • Hannah Y. Wen
    • 1
  1. 1.Department of PathologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  4. 4.Lilly Oncology, Eli Lilly and CompanyNew YorkUSA
  5. 5.Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA

Personalised recommendations